Clinical Epigenetics:DNA甲基化檢測或可幫助預測乳腺癌復發

2015年9月25日訊/生物谷BIOON/-發表在今天《臨床實驗胚胎學》雜誌上的新研究表明有一種簡單的血液測試方法可以確定癌症侵犯其他器官如肺、骨頭或大腦等疾病復發的風險。這樣的測試對改善所有類型的女性乳腺癌會產生深遠影響，這種疾病會影響八分之一的女性。

在研究中，翻譯基因組學研究院(TGen)的研究人員確定了21 DNA甲基化熱點——隨著30億化學鹼基的DNA甲基化水平增加，可能有轉移性乳腺癌的存在。

「這些發現可能導致一個高度敏感的血液測試面板-一種液體活檢可以幫助改善乳腺癌患者的治療。」Bodour Salhia博士說。

「這種21-gene是一種潛在的生物標誌物，可能表明患者乳房或身體的其它部位癌症復發處於高危狀態，患者可能受益於附加的治療來消除疾病復發的可能。」Salhia博士說。「這將是至關重要的信息，因為他們會考慮術後持續治療或完成每一輪化療的情況。」

生物標誌物是指標分子，如蛋白質或DNA，他們在血液、體液或組織樣本中是可測的，可以用來診斷或衡量一個特定疾病或給定治療的影響。

利用全基因組測序，研究人員從40例轉移性乳腺癌患者的血液樣本中尋找生物標記的DNA游離鏈(cfDNA)循環池，並將他們與40例健康個體和40例無病乳腺癌復發的倖存者進行比較。

研究結果表明，儘管來自現行的其他基因特徵的巨大數量信息是可用的，但沒有一個可以精確地預測個體的臨床過程，它們依賴於組織存在，出現在一個單一的時間點。有患者認為用標準治療高風險疾病做得很好，且從不復發。

相比之下，TGen研究發現 21基因被「差異甲基化」——這意味著他們可能會改變甲基化水平——與健康個體和癌症倖存者相比，所有這些在轉移性乳腺癌患者體內會持續升高。

下一步我們會確證使用個體樣本的結果。（生物谷Bioon.com）

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Whole-genome bisulfite sequencing of cell-free DNA identifies signature associated with metastatic breast cancer

Christophe Legendre†, Gerald C. Gooden†, Kyle Johnson, Rae Anne Martinez, Winnie S. Liang and Bodour Salhia*

A number of clinico-pathological criteria have been established as breast cancer prognostic markers to determine risk of recurrence and stratify patients into high- and low-risk groups. The likelihood of distant metastasis increases with tumor size, the presence and number of lymph-node involvement (≥4 nodes have a higher recurrence risk), lack of estrogen receptor (ER) expression, over-expression of Her2, a high proliferative index, lymphovascular invasion, and loss of histopathological differentiation [1]. Molecular profiles have improved our ability to determine the need of chemotherapy for those individuals who are deemed high-risk. The most widely used multigene classifiers include the 21-gene Oncotype Dx signature (Genomic Health, USA), the 70-gene MammaPrint signature (Agendia, Netherlands), the 76-gene Rotterdam signature, and the PAM50 intrinsic classifier (NanoString, USA) [2]. Despite the huge quantity of information gleaned from these gene signatures, none can precisely predict the clinical course of an individual and rely on the presence of tissue at a single time point. Therefore, they are not able to monitor a patient’s risk status after completion of therapy due to residual disease. Even with the clinico-pathological features, there are patients deemed high-risk who do very well with standard therapy and never experience a recurrence and patients with low-risk profiles who still die of breast cancer. There also remains a risk of recurrence even after the most effective chemotherapy agents are administered to high-risk patients. We report a 21-gene DNA hypermethylation signature, detectable in the circulation of MBC patients, which maybe useful in the pre-macrometastatic setting to indicate patients at a high risk of recurrence.